Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects
This study has been terminated.
Sponsor:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00706797
First received: June 25, 2008
Last updated: June 16, 2011
Last verified: June 2011
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Purpose
To assess comparative radiographic efficacy, clinical efficacy and safety of etanercept (ETN) + methotrexate (MTX) with usual disease-modifying anti-rheumatic drug (DMARD) treatment in subjects with moderate RA who were treated with MTX monotherapy, but continue to have moderate disease activity.
| Condition | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Drug: etanercept (EnbrelTM) Drug: methotrexate |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open-Label, Randomized Study to Evaluate the Radiographic Efficacy and Safety of Enbrel™ (Etanercept) Added to Methotrexate in Comparison With Usual Treatment in Subjects With Moderate Rheumatoid Arthritis Disease Activity |
Resource links provided by NLM:
Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:
Primary Outcome Measures:
- Change From Baseline in Modified Total Sharp Score (TSS) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Secondary Outcome Measures:
- Change From Baseline in Erosions at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
- Change From Baseline in Joint Space Narrowing at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]Joint space narrowing score (a component of the modified TSS) is a measure of change in joint health. Joint space narrowing score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
- Percentage of Participants Showing no Radiographic Progression (TSS Change <0.5) at Week 52 [ Time Frame: Baseline, Week 52, Last observation carried forward (LOCF) ] [ Designated as safety issue: No ]Radiographic non-progression determined based on TSS change <0.5 using the dichotomous response Yes / No. The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
- Percentage of Participants Achieving >1.2 Improvement in Disease Activity Score Based on a 28-joint Count (DAS28) [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using Visual Analog Scale (VAS); range 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 square root (√) (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.1=higher disease activity; <3.2=low disease activity; <2.6=clinical remission. Achievement of >1.2 improvement defined as decrease in DAS28 >1.2 (change in DAS28 < -1.2).
- Percentage of Participants Achieving Remission (DAS28 <2.60) [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.
- Percentage of Participants Achieving Low Disease Activity (DAS28 ≤3.20) [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.
- Percentage of Participants Achieving a >0.6 Disease Activity Score (DAS)28 Response [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and participant's assessment of general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission. DAS28 response of >0.6 defined as decrease in DAS28 >0.6 (change in DAS28 < -0.6).
- Percentage of Participants Achieving Moderate or Good Response on European League Against Rheumatism (EULAR) Response Criteria [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]Response to treatment assessed by EULAR response criteria. Participants were characterized as good, moderate, or non-responders based on both Disease Activity Score (DAS) level attained and change in DAS. Good response defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders = participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >5.1. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.
- Percentage of Participants With American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]American College of Rheumatology 20% (ACR20) response: responder = ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
- Percentage of Participants With American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]American College of Rheumatology 50% (ACR50) response: responder = ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
- Percentage of Participants With American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]American College of Rheumatology 70% (ACR70) response: responder = ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR) . Subjects withdrawing early were non-responders.
- Percentage of Participants With American College of Rheumatology 90% (ACR90) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]American College of Rheumatology 90% (ACR 90) response: responder = ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
- Change From Baseline in Mean Daily Dose of Corticosteroids to Manage Flare-ups Across the 52-week Treatment Period [ Time Frame: Week 4, Week 12, Week 24, Week 40, Week 52 ] [ Designated as safety issue: No ]Mean daily dose of corticosteroids to manage flare-ups (temporary increases in corticosteroid dose or use of intra-articular steroids) during treatment period. Daily dose of equivalent prednisone derived in mg/day: oral corticosteroids: 5 mg of prednisone = 5 mg of prednisolone = 25 mg of cortisone = 20 mg of hydrocortisone = 4 mg of methylprednisolone = 4 mg of triamcinolone = 2mg of paramethasone = 0.75 mg of betamethasone = 0.75 of dexamethasone = 0.3 of cortivazol.
- Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII) [ Time Frame: Week 12, Week 52 ] [ Designated as safety issue: No ]Participants were asked how their pain had been during the last 48 hours compared to baseline. Participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.
- Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) [ Time Frame: Week 4, Week 12, Week 24, Week 40, Week 52 ] [ Designated as safety issue: No ]Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours.
- Health Related Quality of Life: EuroQol-5D Health Index [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.
- Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
| Enrollment: | 141 |
| Study Start Date: | September 2008 |
| Study Completion Date: | May 2010 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Usual care
Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).
|
Drug: methotrexate |
|
Active Comparator: ETN + MTX
Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
|
Drug: etanercept (EnbrelTM) Drug: methotrexate |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis.
- Documented evidence, confirmed by a blinded 3rd party assessor, of at least one erosion observed by X-ray at randomization based on X-ray taken at the screening visit.
- Have received MTX as stable dose for 28 days prior to the screening visit.
Exclusion Criteria:
- Previous treatment with ETN, infliximab, adalimumab, other Tumor necrosis factor (TNF) -a inhibitors, anakinra or other biological agents.
- Receipt of any DMARD, other than MTX, within 28 days before screening.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00706797
Show 49 Study Locations
Show 49 Study LocationsSponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Wyeth is now a wholly owned subsidiary of Pfizer |
More Information
No publications provided by Wyeth is now a wholly owned subsidiary of Pfizer
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Director, Clinical Trial Disclosure Group, Wyeth |
| ClinicalTrials.gov Identifier: | NCT00706797 History of Changes |
| Other Study ID Numbers: | 0881X1-4437 |
| Study First Received: | June 25, 2008 |
| Results First Received: | December 22, 2010 |
| Last Updated: | June 16, 2011 |
| Health Authority: | Australia: National Health and Medical Research Council |
Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
|
Moderate Rheumatoid Arthritis |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Methotrexate TNFR-Fc fusion protein Antirheumatic Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs |
Pharmacologic Actions Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Nucleic Acid Synthesis Inhibitors Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics |
ClinicalTrials.gov processed this record on May 23, 2013